Andrew Davis is an undergraduate student majoring in pharmaceutical sciences at College of Pharmacy, The Ohio State University.
Genetic alterations of RDINK4/ARF enhancer in human cancer cells
Article first published online: 12 OCT 2012
© 2013 Wiley Periodicals, Inc.
Volume 53, Issue 3, pages 211–218, March 2014
How to Cite
Li, J., Knobloch, T. J., Poi, M. J., Zhang, Z., Davis, A. T., Muscarella, P. and Weghorst, C. M. (2014), Genetic alterations of RDINK4/ARF enhancer in human cancer cells. Mol. Carcinog., 53: 211–218. doi: 10.1002/mc.21965
- Issue published online: 21 FEB 2014
- Article first published online: 12 OCT 2012
- Manuscript Accepted: 29 AUG 2012
- Manuscript Revised: 25 AUG 2012
- Manuscript Received: 12 APR 2012
- RD enhancer;
- the INK4/ARF locus;
- genetic alteration
Recent identification of an enhancer element, RDINK4/ARF (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15INK4B (p15), p14ARF, and p16INK4A (p16) tumor suppressor genes. While genetic inactivation of p15, p14ARF, and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15, p14ARF, and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using real-time PCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15, p14ARF, and p16. Furthermore, the status of RD was poorly associated with the expression of p15, p14ARF, and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored. © 2012 Wiley Periodicals, Inc.